Organocatalytic asymmetric Friedel–Crafts alkylation/hemiketalization/lactonization cascade reactions: highly enantioselective synthesis of furo[2,3-b]benzofuranones

Abstract

An efficient asymmetric organocatalytic Friedel–Crafts alkylation/hemiketalization/lactonization cascade reaction of 3-ylidene oxindoles with 2-naphthols and activated phenols has been developed. In the presence of 5 mol% of a bifunctional squaramide catalyst, this scalable cascade reaction affords a series of novel furo[2,3-b]benzofuranone derivatives with three adjacent stereogenic centers in good to excellent yields (up to 91%) and with high stereoselectivities (up to 96% ee, >20 : 1 d.r.). Moreover, this cascade reaction provides a distinct lactonization process of amide functional groups under mild reaction conditions to access the diversely decorated furo[2,3-b]benzofuranones of considerable importance to natural product synthesis and medicinal chemistry.